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Animal experiments were conducted in accordance with the UCLA Animal Research Committee. Statistics were performed using Student��s t test (two groups) or ANOVA (greater than two groups), with post hoc tests to compare to the buy Fludarabine control group. Data are presented as means?�� SEM or means?�� SD, as indicated, and considered statistically significant at p?Onalespib supplier not including the energy expended during the biosynthesis of rRNA (Buttgereit and Brand, 1995?and?Rolfe and Brown, 1997). Mitochondria are the main producers of ATP under physiological conditions in mammals and play a critical role in overall energy balance (Vander Heiden et?al., 2009). The mechanistic/mammalian target of rapamycin (mTOR) is a serine/threonine kinase that has been implicated in a variety of physiological processes and pathological states (Zoncu et?al., 2011). mTOR forms two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which differ in their composition, downstream targets, regulation, and sensitivity to the allosteric inhibitor rapamycin (Hara et?al., 2002, Kim et?al., 2002?and?Sarbassov et?al., 2004). mTORC1 stimulates mRNA translation and other anabolic processes (e.g., lipogenesis) in response to a variety of extracellular signals and intracellular cues such as nutrients, oxygen, and hormones (Laplante and Sabatini, 2012?and?Yecies and Manning, 2011). mTORC2 controls cell survival, cytoskeleton organization (Jacinto et?al., 2004?and?Sarbassov et?al., 2004), lipogenesis, and gluconeogenesis (Hagiwara et?al., 2012?and?Yuan et?al., 2012) by activating AGC kinases including serum- and glucocorticoid-regulated kinase (SGK) and AKT (Garc��a-Mart��nez and Alessi, 2008, Ikenoue et?al., 2008?and?Sarbassov et?al., 2005). Hyperactivation of mTORC1 frequently accompanies diseases characterized by perturbations in energy metabolism and translation including cancer and the metabolic syndrome (Laplante and Sabatini, 2012). mTORC1 Dabigatran stimulates translation by phosphorylating downstream targets including 4E-BPs and ribosomal protein S6 kinases (S6Ks) (Roux and Topisirovic, 2012). Phosphorylation of 4E-BPs by mTORC1 leads to their dissociation from eIF4E, thereby allowing association of eIF4E with eIF4G and the assembly of the eIF4F translation initiation complex at the mRNA 5�� end (Gingras et?al., 1999, Gingras et?al., 2001?and?Pause et?al., 1994). S6Ks phosphorylate components of the translational machinery and associated factors such as ribosomal protein S6, eIF4B, and PDCD4 (Banerjee et?al., 1990, Dorrello et?al., 2006, Kozma et?al.